Best Practice & Research Clinical Endocrinology & Metabolism
Volume 21, Issue 2 , Pages 173-191 , June 2007

Thyroid hormone transporters in health and disease: advances in thyroid hormone deiodination

  • Josef Köhrle, PhD (Director)

      Affiliations

    • Corresponding Author InformationTel.: +49 (0)30 450 524021; Fax: +49 (0)30 450 524922.

References 

  1. Yen PM, Ando S, Feng X, et al. Thyroid hormone action at the cellular, genomic and target gene levels. Molecular and Cellular Endocrinology. 2006;246:121–127
  2. Psarra AMG, Solakidi S, Sekeris CE. The mitochondrion as a primary site of action of steroid and thyroid hormones: presence and action of steroid and thyroid hormone receptors in mitochondria of animal cells. Molecular and Cellular Endocrinology. 2006;246:21–33
  3. Silva JE. Thermogenic mechanisms and their hormonal regulation. Physiological Reviews. 2006;86:435–464
  4. Mousa SA, O'Connor L, Davis FB, et al. Proangiogenesis action of the thyroid hormone analog 3,5-diiodothyropropionic acid (ditpa) is initiated at the cell surface and is integrin mediated. Endocrinology. 2006;147:1602–1607
  5. Farwell AP, Dubord-Tomasetti SA, Pietrzykowski AZ, et al. Dynamic non-genomic actions of thyroid hormone in the developing rat brain. Endocrinology. 2006;147:2567–2574
  6. Hart ME, Suchland KL, Miyakawa M, et al. Trace amine-associated receptor agonists: synthesis and evaluation of thyronamines and related analogues. Journal of Medicinal Chemistry. 2006;49:1101–1112
  7. Chiellini G, Frascarelli S, Ghelardoni S, et al. Cardiac effects of 3-iodothyronamine: a new aminergic system modulating cardiac function. The FASEB Journal. 2007;21:1597–1608
  8. Dunn JT, Dunn AD. Update on intrathyroidal iodine metabolism. Thyroid. 2001;11:407–414
  9. Köhrle J, Jakob F, Contempré B, et al. Selenium, the thyroid, and the endocrine system. Endocrine Reviews. 2005;26:944–984
  10. Kohrle J. Selenium and the control of thyroid hormone metabolism. Thyroid. 2005;15:841–853
  11. Beckett GJ, Beech S, Nicol F, et al. Species differences in thyroidal iodothyronine deiodinase expression and the effect of selenium deficiency on its activity. Journal of Trace Elements and Electrolytes in Health and Disease. 1993;7:123–124
  12. Maia AL, Kim BW, Huang SA, et al. Type 2 iodothyronine deiodinase is the major source of plasma T3 in euthyroid humans. The Journal of Clinical Investigation. 2005;115:2524–2533
  13. Jakobs T, Schmutzler C, Meissner J, et al. The promotor of the human type I 5′-deiodinase gene: mapping of the transcription start site and identification of a DR+4 thyroid hormone responsive element. European Journal of Biochemistry. 1997;247:288–297
  14. Bianco AC, Kim BW. Deiodinases: implications of the local control of thyroid hormone action. The Journal of Clinical Investigation. 2006;116:2571–2579
  15. Bianco AC, Salvatore D, Gereben B, et al. Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocrine Reviews. 2002;23:38–89
  16. Ambroziak M, Pachucki J, Chojnowski K, et al. Pax-8 expression correlates with Type II 5′ deiodinase expression in thyroids from patients with Graves' disease. Thyroid. 2003;13:141–148
  17. Laurberg P. Iodothyronine secretion from perfused dog thyroid lobes after prolonged thyrotropin treatment in vivo. Endocrinology. 1981;109:1560–1565
  18. Selmi-Ruby S, Rousset B. Analysis of the functional state of T3 nuclear receptors expressed in thyroid cells. Molecular and Cellular Endocrinology. 1996;119:95–104
  19. Friesema EC, Jansen J, Heuer H, et al. Mechanisms of disease: psychomotor retardation and high T3 levels caused by mutations in monocarboxylate transporter 8. Nature Clinical Practice. Endocrinology & Metabolism. 2006;2:512–523
  20. Leonard JL, Visser TJ, Leonard DM. Characterization of the subunit structure of the catalytically active type I iodothyronine deiodinase. The Journal of Biological Chemistry. 2001;276:2600–2607
  21. Curcio-Morelli C, Gereben B, Zavacki AM, et al. In vivo dimerization of Types 1, 2, and 3 iodothyronine selenodeiodinases. Endocrinology. 2003;144:937–946
  22. Leonard JL, Simpson G, Leonard DM. Characterization of the protein dimerization domain responsible for assembly of functional selenodeiodinases. The Journal of Biological Chemistry. 2005;280:11093–11100
  23. Simpson GIC, Leonard DM, Leonard JL. Identification of the key residues responsible for the assembly of selenodeiodinases. The Journal of Biological Chemistry. 2006;281:14615–14621
  24. Zeold A, Pormuller L, Dentice M, et al. Metabolic instability of type 2 deiodinase is transferable to stable proteins independently of subcellular localization. The Journal of Biological Chemistry. 2006;281:31538–31543
  25. Kuiper GG, Klootwijk W, Visser TJ. Expression of recombinant membrane-bound type I iodothyronine deiodinase in yeast. Journal of Molecular Endocrinology. 2005;34:865–878
  26. Montero-Pedrazuela A, Bernal J, Guadano-Ferraz A. Divergent expression of type 2 deiodinase and the putative thyroxine- binding protein p29, in rat brain, suggests that they are functionally unrelated proteins. Endocrinology. 2003;144:1045–1052
  27. Köhrle J, Baur A, Winzer R, et al. Expression of type II 5′-deiodinase (5′DII) and plasma glutathione peroxidase (pGPx) in human thyroid. Endocrine Journal. 2000;47(Supplement):175
  28. Ohba K, Yoshioka T, Muraki T. Identification of two novel splicing variants of human type II iodothyronine deiodinase mRNA. Molecular and Cellular Endocrinology. 2001;172:169–175
  29. Kasahara T, Tsunekawa K, Seki K, et al. Regulation of iodothyronine deiodinase and roles of thyroid hormones in human coronary artery smooth muscle cells. Atherosclerosis. 2006;186:207–214
  30. Maeda A, Toyoda N, Yasuzawa-Amano S, et al. Type 2 deiodinase expression is stimulated by growth factors in human vascular smooth muscle cells. Molecular and Cellular Endocrinology. 2003;200:111–117
  31. Friesema EC, Kuiper GG, Jansen J, et al. Thyroid hormone transport by the human monocarboxylate transporter 8 and its rate-limiting role in intracellular metabolism. Molecular Endocrinology. 2006;20:2761–2772
  32. Nicoloff JT, Lum SM, Spencer CA, et al. Peripheral autoregulation of thyroxine to triiodothyronine conversion in man. Hormone and Metabolic Research. Supplement Series. 1984;14:74–79
  33. Nguyen TT, Chapa F, DiStefano JJ. Direct measurement of the contributions of type I and type II 5′-deiodinases to whole body steady state 3,5,3′-triiodothyronine production from thyroxione in the rat. Endocrinology. 1998;139:4626–4633
  34. Leonard JL, Köhrle J. Intracellular pathways of thyroid hormone metabolism. In:  Braverman LE,  Utiger RD editor. Werner and Ingbar's The Thyroid – A Fundamental and Clinical Text. 8th edn.. Philadelphia: J.B. Lippincott Company; 2000;p. 136–173
  35. Schomburg L, Riese C, Michaelis M, et al. Synthesis and metabolism of thyroid hormones is preferentially maintained in selenium-deficient transgenic mice. Endocrinology. 2006;147:1306–1313
  36. Streckfuss F, Hamann I, Schomburg L, et al. Hepatic deiodinase activity is dispensable for the maintenance of normal circulating thyroid hormone levels in mice. Biochemical and Biophysical Research Communications. 2005;337:739–745
  37. Chanoine JP, Braverman LE, Farwell AP, et al. The thyroid gland is a major source of circulating T3 in the rat. The Journal of Clinical Investigation. 1993;91:2709–2713
  38. Köhrle J. Iodothyronine deiodinases. Methods in Enzymology. 2002;347:125–167
  39. Ziouzenkova O, Orasanu G, Sukhova G, et al. Asymmetric cleavage of beta-carotene yields a transcriptional repressor of retinoid X receptor and peroxisome proliferator-activated receptor responses. Molecular Endocrinology. 2007;21:77–88
  40. Kuiper GGJM, Wassen F, Klootwijk W, et al. Molecular basis for the substrate selectivity of cat Type I iodothyronine deiodinase. Endocrinology. 2003;144:5411–5421
  41. Hatfield DL, Gladyshev VN. How selenium has altered our understanding of the genetic code. Molecular and Cellular Biology. 2002;22:3565–3576
  42. Sun X, Maquat LE. Nonsense-mediated decay: assaying for effects on selenoprotein mRNAs. Methods in Enzymology. 2002;347:49–57
  43. Muller C, Wingler K, Brigelius-Flohe R. 3′UTRs of glutathione peroxidases differentially affect selenium-dependent mRNA stability and selenocysteine incorporation efficiency. Biological Chemistry. 2003;384:11–18
  44. Riese C, Michaelis M, Mentrup B, et al. Selenium-dependent pre- and posttranscriptional mechanisms are responsible for sexual dimorphic expression of selenoproteins in murine tissues. Endocrinology. 2006;147:5883–5892
  45. Dumitrescu AM, Liao XH, Abdullah MS, et al. Mutations in SECISBP2 result in abnormal thyroid hormone metabolism. Nature Genetics. 2005;37:1247–1252
  46. Curcio C, Baqui MM, Salvatore D, et al. The human type 2 iodothyronine deiodinase is a selenoprotein highly expressed in a mesothelioma cell line. The Journal of Biological Chemistry. 2001;276:30183–30187
  47. Kim BW, Daniels GH, Harrison BJ, et al. Overexpression of Type 2 iodothyronine deiodinase in follicular carcinoma as a cause of low circulating free thyroxine levels. The Journal of Clinical Endocrinology and Metabolism. 2003;88:594–598
  48. Köhrle J. Thyroid carcinoma: interrelationships between local thyroid hormone metabolism by the type I 5′-deiodinase and the expression of thyroid hormone receptors and other thyroid-specific (de-)differentiation markers. Current Topics in Pathology. 1997;91:83–116
  49. Schmutzler C, Köhrle J. Retinoic acid redifferentiation therapy for thyroid cancer. Thyroid. 2000;10:393–406
  50. Schmutzler C, Hoang-Vu C, Ruger B, et al. Human thyroid carcinoma cell lines show different retinoic acid receptor repertoires and retinoid responses. European Journal of Endocrinology. 2004;150:547–556
  51. Huang SA, Fish SA, Dorfman DM, et al. A 21-year-old woman with consumptive hypothyroidism due to a vascular tumor expressing Type 3 iodothyronine deiodinase. The Journal of Clinical Endocrinology and Metabolism. 2002;87:4457–4461
  52. Draper N, Stewart PM. 11beta-hydroxysteroid dehydrogenase and the pre-receptor regulation of corticosteroid hormone action. The Journal of Endocrinology. 2005;186:251–271
  53. Masuda S, Strugnell SA, Knutson JC, et al. Evidence for the activation of 1alpha-hydroxyvitamin D(2) by 25-hydroxyvitamin D-24-hydroxylase: Delineation of pathways involving 1alpha,24-dihydroxyvitamin D(2) and 1alpha,25-dihydroxyvitamin D(2). Biochimica et Biophysica Acta. 2006;1761:221–234
  54. Mindnich R, Moller G, Adamski J. The role of 17 beta-hydroxysteroid dehydrogenases. Molecular and Cellular Endocrinology. 2004;218:7–20
  55. Bookout AL, Jeong Y, Downes M, et al. Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional network. Cell. 2006;126:789–799
  56. Qatanani M, Zhang J, Moore DD. Role of the constitutive androstane receptor in xenobiotic-induced thyroid hormone metabolism. Endocrinology. 2005;146:995–1002
  57. De Groot LJ. Dangerous dogmas in medicine: the nonthyroidal illness syndrome. The Journal of Clinical Endocrinology and Metabolism. 1999;84:151–164
  58. Boelen A, Wiersinga WM, Koehrle J. Contributions of cytokines to nonthyroidal illness. Current Opinion in Endocrinology and Diabetes. 2006;13:444–450
  59. Hesch RD. The ‘Low T3-Syndrome’. London: Academic Press; 1981;pp. 1–263
  60. Peeters RP, Debaveye Y, Fliers E, et al. Changes within the thyroid axis during critical illness. Critical Care Clinics. 2006;22:41–55
  61. Boelen A, Kwakkel J, Alkemade A, et al. Induction of type 3 deiodinase activity in inflammatory cells of mice with chronic local inflammation. Endocrinology. 2005;146:5128–5134
  62. Peeters RP, Kester MH, Wouters PJ, et al. Increased thyroxine sulfate levels in critically ill patients as a result of a decreased hepatic type I deiodinase activity. The Journal of Clinical Endocrinology and Metabolism. 2005;90:6460–6465
  63. Wu SY, Green WL, Huang WS, et al. Alternate pathways of thyroid hormone metabolism. Thyroid. 2005;15:943–958
  64. Angstwurm MWA, Schottdorf J, Schopohl J, et al. Selenium replacement in patients with severe systemic inflammatory response syndrome improves clinical outcome. Critical Care Medicine. 1999;27:1807–1813
  65. Fekete C, Singru PS, Sarkar S, et al. Ascending brainstem pathways are not involved in lipopolysaccharide-induced suppression of thyrotropin-releasing hormone gene expression in the hypothalamic paraventricular nucleus. Endocrinology. 2005;146:1357–1363
  66. Alkemade A, Friesema EC, Kuiper GG, et al. Novel neuroanatomical pathways for thyroid hormone action in the human anterior pituitary. European Journal of Endocrinology. 2006;154:491–500
  67. Baur A, Bauer K, Jarry H, et al. Effects of proinflammatory cytokines on anterior pituitary 5′- deiodinase type I and type II. The Journal of Endocrinology. 2000;167:505–515
  68. Boelen A, Kwakkel J, Platvoet-Ter Schiphorst M, et al. Contribution of interleukin-12 to the pathogenesis of non-thyroidal illness. Hormone and Metabolic Research. 2004;36:101–106
  69. Baur A, Buchfelder M, Köhrle J. Expression of 5′-deiodinase enzymes in normal pituitaries and in various human pituitary adenomas. European Journal of Endocrinology. 2002;147:263–268
  70. Christoffolete MA, Ribeiro R, Singru P, et al. Atypical expression of type 2 iodothyronine deiodinase in thyrotrophs explains the thyroxine-mediated pituitary thyrotropin feedback mechanism. Endocrinology. 2006;147:1735–1743
  71. Boelen A, Kwakkel J, Wiersinga WM, et al. Chronic local inflammation in mice results in decreased TRH and type 3 deiodinase mRNA expression in the hypothalamic paraventricular nucleus independently of diminished food intake. The Journal of Endocrinology. 2006;191:707–714
  72. Tannahill LA, Visser TJ, McCabe CJ, et al. Dysregulation of iodothyronine deiodinase enzyme expression and function in human pituitary tumours. Clinical Endocrinology. 2002;56:735–743
  73. Heuer H, Maier MK, Iden S, et al. The monocarboxylate transporter 8 linked to human psychomotor retardation is highly expressed in thyroid hormone sensitive neuron populations. Endocrinology. 2005;146:1701–1706
  74. Bernal J. Role of monocarboxylate anion transporter 8 (MCT8) in thyroid hormone transport: answers from mice. Endocrinology. 2006;147:4034–4035
  75. Jakobs TC, Mentrup B, Schmutzler C, et al. Proinflammatory cytokines inhibit the expression and function of human type I 5′-deiodinase in HepG2 hepatocarcinoma cells. European Journal of Endocrinology. 2002;146:559–566
  76. Koenig RJ. Regulation of type 1 iodothyronine deiodinase in health and disease. Thyroid. 2005;15:835–840
  77. Kwakkel J, Wiersinga WM, Boelen A. Differential involvement of nuclear factor-{kappa}B and activator protein-1 pathways in the interleukin-1{beta}-mediated decrease of deiodinase type 1 and thyroid hormone receptor {beta}1 mRNA. The Journal of Endocrinology. 2006;189:37–44
  78. Zeold A, Doleschall M, Haffner MC, et al. Characterization of the nuclear factor-kappa B responsiveness of the human dio2 gene. Endocrinology. 2006;147:4419–4429
  79. Yu J, Koenig RJ. Induction of type 1 iodothyronine deiodinase to prevent the nonthyroidal illness syndrome in mice. Endocrinology. 2006;147:3580–3585
  80. Forhead AJ, Curtis K, Kaptein E, et al. Developmental control of iodothyronine deiodinases by cortisol in the ovine fetus and placenta near term. Endocrinology. 2006;147:5988–5994
  81. Grarup N, Andersen MK, Andreasen CH, et al. Studies of the common DIO2 Thr92Ala polymorphism and metabolic phenotypes in 7,342 Danish whites. The Journal of Clinical Endocrinology and Metabolism. 2007;92:363–366
  82. Mentuccia D, Thomas MJ, Coppotelli G, et al. The Thr92Ala deiodinase Type 2 (DIO2) variant is not associated with Type 2 diabetes or indices of insulin resistance in the old order of Amish. Thyroid. 2005;15:1223–1227
  83. Canani LH, Capp C, Dora JM, et al. The type 2 deiodinase A/G (Thr92Ala) polymorphism is associated with decreased enzyme velocity and increased insulin resistance in patients with type 2 diabetes mellitus. The Journal of Clinical Endocrinology and Metabolism. 2005;90:3472–3478
  84. Appelhof BC, Peeters RP, Wiersinga WM, et al. Polymorphisms in type 2 deiodinase are not associated with well-being, neurocognitive functioning, and preference for combined thyroxine/3,5,3′-triiodothyronine therapy. The Journal of Clinical Endocrinology and Metabolism. 2005;90:6296–6299
  85. Eisenberg M, Samuels M, DiStefano JJ. L-T4 bioequivalence and hormone replacement studies via feedback control simulations. Thyroid. 2006;16:1279–1292
  86. Peeters RP, van der Deure WM, Visser TJ. Genetic variation in thyroid hormone pathway genes; polymorphisms in the TSH receptor and the iodothyronine deiodinases. European Journal of Endocrinology. 2006;155:655–662
  87. Brabant G, Beck-Peccoz P, Jarzab B, et al. Is there a need to redefine the upper normal limit of TSH?. European Journal of Endocrinology. 2006;154:633–637
  88. Volzke H, Alte D, Kohlmann T, et al. Reference intervals of serum thyroid function tests in a previously iodine-deficient area. Thyroid. 2005;15:279–285
  89. Weitzel JM, Iwen KA, Seitz HJ. Regulation of mitochondrial biogenesis by thyroid hormone. Quarterly Journal of Experimental Physiology. 2003;88:121–128
  90. Barker SB, Klitgaard HM. Metabolism of tissues excised from thyroxine-injected rats. The American Journal of Physiology. 1952;170:81–86
  91. Hansen JB, Kristiansen K. Regulatory circuits controlling white versus brown adipocyte differentiation. The Biochemical Journal. 2006;398:153–168
  92. Cinti S. The role of brown adipose tissue in human obesity. Nutrition, Metabolism and Cardiovascular Diseases. 2006;16:569–574
  93. Watanabe M, Houten SM, Mataki C, et al. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature. 2006;439:484–489
  94. Lechan RM, Fekete C. The TRH neuron: a hypothalamic integrator of energy metabolism. In:  Kalsbeek A editors. Progress in Brain Research Hypothalamic Integration of Energy Metabolism, Proceedings of the 24th International Summer School of Brain Research, held at the Royal Netherlands Academy of Arts and Sciences. vol. 153:Elsevier; 2006;pp. 209–235
  95. Fliers E, Alkemade A, Wiersinga WM, et al. Hypothalamic thyroid hormone feedback in health and disease. In:  Kalsbeek A editors. Progress in Brain Research Hypothalamic Integration of Energy Metabolism, Proceedings of the 24th International Summer School of Brain Research, held at the Royal Netherlands Academy of Arts and Sciences. vol. 153:Elsevier; 2006;pp. 189–207
  96. Jakobs TC, Koehler MR, Schmutzler C, et al. Structure of the human Type I iodothyronine 5′-deiodinase gene and localization to chromosome 1p32-p33. Genomics. 1997;42:361–363
  97. Celi FS, Canettieri G, Mentuccia D, et al. Structural organization and chromosomal localization of the human type II deiodinase gene. European Journal of Endocrinology. 2000;143:267–271
  98. Hernandez A, Park JP, Lyon GJ, et al. Localization of the type 3 iodothyronine deiodinase (DIO3) gene to human chromosome 14q32 and mouse chromosome 12F1. Genomics. 1998;53:119–121
  99. Kim SW, Hong SJ, Kim KM, et al. A Novel cell type-specific mechanism for thyroid hormone-dependent negative regulation of the human type 1 deiodinase gene. Molecular Endocrinology. 2004;18:2924–2936
  100. Hernandez A, St.Germain DL. Activity and response to serum of the mammalian thyroid hormone deiodinase 3 gene promoter: identification of a conserved enhancer. Molecular and Cellular Endocrinology. 2003;206:23–32

PII: S1521-690X(07)00031-0

doi: 10.1016/j.beem.2007.04.001

Best Practice & Research Clinical Endocrinology & Metabolism
Volume 21, Issue 2 , Pages 173-191 , June 2007

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